Emergence of waterfowl‐originated gene cassettes in HPAI H7N9 viruses caused severe human infection in Fujian, China

Yang, Lei; Xie, Jianfeng; Zhang, Ye; Zhu, Wenfei; Li, Xiyan; Wei, Hejiang; Li, Zi; Zhao, Lin; Bo, Hong; Liu, Jia; Dong, Jie; Chen, Tao; Shu, Yuelong; Weng, Yue; Wang, Dayan

doi:10.1111/irv.12657

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…Given that the majority of H7N9 viruses are already resistant to amantadine, the occurrence of additional mutations conferring oseltamivir resistance remains a public concern. The NA R292K mutation was previously identified in some isolates from patients infected with H7N9 and it was suggested to associate with prolonged virus shedding and adverse clinical outcomes (32,33). It…”

Section: Discussionmentioning

confidence: 99%

Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice

et al. 2021

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Background: Avian influenza A (H7N9) virus has caused more than 1,500 cases of human infection since its emergence in early 2013. Displaying little or no pathogenicity in poultry, but a 40% case-fatality rate in humans, five waves of H7N9 human infections occurred in China during 2013-2017, caused solely by a low pathogenicity strain. However, avian isolates possessing a polybasic connecting peptide in the hemagglutinin (HA) protein were detected in mid-2016, indicating that a highly pathogenic virus had emerged and was cocirculating with the low pathogenicity strains.Methods: Here we characterize the pathogenicity of a newly emerged human H7N9 variant with a PEVPKRKRTAR/GLF insertion motif at the cleavage site of the HA protein in vitro and in vivo.Results: This variant replicates in MDCK cells independently of TPCK-trypsin, which is indicative of high pathogenicity in chickens. The 50% mouse lethal dose (MLD 50 ) of this novel isolate was less than 10 plaque forming units (PFU), compared with 3.16×10 4 for an identical virus lacking the polybasic insertion, indicating a high virulence phenotype.Conclusions: Our results demonstrate that the multiple basic amino acid insertion in the HA protein of the H7N9 variant confers high virulence in mammals, highlighting a potential risk to humans. Continuous viral surveillance is therefore necessary in the China region to improve pandemic preparedness.

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Section: Discussionmentioning

confidence: 99%

Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice

et al. 2021

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“…The six internal genes of the H7N9 virus were derived from at least two different H9N2 virus lineages, and the H7 and N9 genes came from wild birds [13][14][15][16][17]. Nonetheless, the H7N9 virus has continually undergone reassortment with other subtypes of AIVs since its emergence, such as seasonal influenza A virus H1N1, H3N2, and even influenza B virus [18][19][20], H5N6 [21,22], H6Ny [22,23], H9N2 [23][24][25][26][27][28], and even H7N9 itself [29]. As a result, multiple novel viruses were generated, including H7N2 [30], H7N3 [31], H7N4 [32], and H7N6 [33].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Reassortment Analysis of Influenza A H7N9 Viruses Circulating in China during 2013–2019

Wang

et al. 2022

Viruses

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Reassortment with the H9N2 virus gave rise to the zoonotic H7N9 avian influenza virus (AIV), which caused more than five outbreak waves in humans, with high mortality. The frequent exchange of genomic segments between H7N9 and H9N2 has been well-documented. However, the reassortment patterns have not been described and are not yet fully understood. Here, we used phylogenetic analyses to investigate the patterns of intersubtype and intrasubtype/intralineage reassortment across the eight viral segments. The H7N9 virus and its progeny frequently exchanged internal genes with the H9N2 virus but rarely with the other AIV subtypes. Before beginning the intrasubtype/intralineage reassortment analyses, five Yangtze River Delta (YRD A-E) and two Pearl River Delta (PRD A-B) clusters were divided according to the HA gene phylogeny. The seven reset segment genes were also nomenclatured consistently. As revealed by the tanglegram results, high intralineage reassortment rates were determined in waves 2–3 and 5. Additionally, the clusters of PB2 c05 and M c02 were the most dominant in wave 5, which could have contributed to the onset of the largest H7N9 outbreak in 2016–2017. Meanwhile, a portion of the YRD-C cluster (HP H7N9) inherited their PB2, PA, and M segments from the co-circulating YRD-E (LP H7N9) cluster during wave 5. Untanglegram results revealed that the reassortment rate between HA and NA was lower than HA with any of the other six segments. A multidimensional scaling plot revealed a robust genetic linkage between the PB2 and PA genes, indicating that they may share a co-evolutionary history. Furthermore, we observed relatively more robust positive selection pressure on HA, NA, M2, and NS1 proteins. Our findings demonstrate that frequent reassortment, particular reassorted patterns, and adaptive mutations shaped the H7N9 viral genetic diversity and evolution. Increased surveillance is required immediately to better understand the current state of the HP H7N9 AIV.

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“…Waterfowls are susceptible to infection by IAVs and serve as natural reservoirs and can spread the viruses to other avian and mammal species. It has been documented that IAV reservoir hosts are important for generating novel reassortant viruses 5–7 …”

Section: Introductionmentioning

confidence: 99%

“…It has been documented that IAV reservoir hosts are important for generating novel reassortant viruses. 5 , 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

Genetic characterization of influenza A virus subtypes H11N6, H11N7, and H11N9 isolated from free‐grazing ducks, Thailand

Chaiyawong

Charoenkul

Udom

et al. 2022

Influenza Resp Viruses

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Influenza A viruses (IAVs) infect avian species and several mammalian species including humans. Anseriformes water birds are an important reservoir of IAVs. In this study, we identified and characterized IAV subtypes H11N6 (n = 5), H11N7 (n = 3), and H11N9 (n = 3) isolated during the influenza surveillance program in free‐grazing ducks from 2012 to 2015 in Thailand. Eleven IAV‐H11 viruses were characterized by either whole genome sequencing (n = 5) or HA and NA gene sequencing (n = 6) for phylogenetic and amino acid analyses. Phylogenetic analysis showed that Thai IAV‐H11 were grouped into Avian Eurasian lineage. Amino acid analysis showed that all Thai IAV‐H11 viruses have low pathogenic avian influenza (LPAI) characteristics and sensitive to Oseltamivir and Amantadine. Novel reassortant viruses (IAV‐H11N7 and IAV‐H11N9) have been observed. The reassortant viruses contained NP, M, and NS gene segments which originate from intercontinental sources which never been reported in Thai IAVs. In summary, this study demonstrated high genetic diversity of IAV‐H11 circulating in free‐grazing ducks. Free‐grazing ducks infected with IAVs generated novel reassortant IAV‐H11. Thus, surveillance of IAVs in free‐grazing ducks should be routinely conducted to monitor novel reassortant viruses and subsequently potential virulence viruses.

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Emergence of waterfowl‐originated gene cassettes in HPAI H7N9 viruses caused severe human infection in Fujian, China

Cited by 9 publications

References 21 publications

Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice

Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice

Genome-Wide Reassortment Analysis of Influenza A H7N9 Viruses Circulating in China during 2013–2019

Genetic characterization of influenza A virus subtypes H11N6, H11N7, and H11N9 isolated from free‐grazing ducks, Thailand

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